Gemfibrozil, or 5-(2,5-dimethylphenoxy)-2,2-dimethylpentanoic acid, is a widely used antihyperlipoproteinemic agent. Physically the chemical is a crystalline material which melts in the range of 61.degree. to 63.degree. C. (hexane) and exhibits a boiling point of 158.degree.-159.degree..sub.0.02 C. The substance is nonhygroscopic and generally compatible with common pharmaceutical excipients but has very poor solubility in water. This is particularly true in a highly acidic medium (such as is encountered in the stomach) since its apparent pKa is 4.7.
The typical daily dose is high, generally about 1200 mg, probably because of the poor water solubility. This dosage generally is administered using for example two capsules of 300 mg or a single compressed tablet of 600 mg, administration in each case being b.i.d.
The present invention pertains to improvements in gemfibrozil formulations which improve the compound's dissolution profile and thus increase the drug's blood levels upon oral administration.
U.S. Pat. No. 4,716,033 discloses a medicament adsorbate such as magnesium aluminum silicate having a medicament, including inter alia gemfibrozil, and surfactant adsorbed thereon.
U.S. Pat. No. 4,753,800 discloses a medicament adsorbate having a medicament, including inter alia gemfibrozil, dispersed in an edible wax adsorbed thereon.
U.S. Pat. No. 4,814,354 discloses pharmaceutical compositions of an anion exchange resin lipid regulator, such as cholestyramine or cholestipol, and gemfibrozil.
U.S. Pat. No. 4,778,676 discloses a chewable confection delivery system of coated cholestyramine and a confectionery matrix..
U.S. Pat. No. 4,816,264 discloses an oral delivery system having a core portion of drug and a cellulosic gelling polymer and a semipermeable membrane around the core.
U.S. Pat. No. 4,865,850 discloses a method of expelling fat from the gastrointestinal tract by administering non-biodegradable collagen particles having fat receptors, including inter alia gemfibrozil, on their surface.
EP-A 295,637 A2 discloses pharmaceutical compositions in which a lipid regulating component, including inter alia gemfibrozil, is combined with inhibitor of acylCoA:cholesterol acyltransferase. EP-A 261,693 A1 discloses a lipid regulating component, including inter alia gemfibrozil, which has been pretreated to render it stale until such time as it reaches the proximal section of the intestines.
PCT WO 88/05296 discloses pharmaceutical compositions in which a lipid regulating component, including inter alia gemfibrozil, is combined with inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase.
Commercially available gemfibrozil capsules contain a small amount of sodium lauryl sulfate, typically less than 0.2%. Compressed tablets of gemfibrozil which are commercially available contain somewhat more but again less than 1%; e.g., 0.7%.